Pygo2通过Pygo2-H3K4me2/3相互作用激活BRPF1,以维持结肠癌恶性进展
Jie Ling1, Zhijie Tang2, Wei Yang2
1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China; Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, Jiangsu, China.
Experimental cell research
|July 9, 2023
概括
皮戈普斯2 (Pygo2) 通过调节BRPF1.1来驱动结肠腺癌 (COAD) 的生长. 针对BRPF1有效抑制Pygo2高的COAD,提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 表观遗传变化对于结肠腺癌 (COAD) 的发展至关重要.
- Pygopus 2 (Pygo2),一个Wnt/b-catenin联合激活剂,与H3K4me2/3相互作用,并影响各种癌症中的染色质重塑.
研究的目的:
- 研究Pygo2-H3K4me2/3协会在COAD进展中的作用和意义.
- 阐明Pygo2在COAD中的功能背后的分子机制.
主要方法:
- 在体外细胞增殖和自我更新的测试.
- 在体内瘤生长和转移模型.
- 路西法酶记者测定和染色体免疫沉 (ChIP) -qPCR测定.
- 在瘤组织中分析Pygo2和BRPF1表达.
- 使用GSK5959.9进行BRPF1的药理抑制.
主要成果:
- 抑制Pygo2减少了COAD细胞的增殖和自我更新;Pygo2的过度表达促进了瘤的生长,迁移和转移.
- 皮戈2与BRPF1表达具有正相关性,并通过H3K4me2/3在促进子上的修饰激活BRPF1转录.
- 在COAD瘤中,Pygo2和BRPF1都高度表达,Pygo2依赖BRPF1驱动COAD进展.
- GSK5959在体外和体内有效抑制Pygo2-高COAD细胞的生长,对Pygo2-低细胞的影响最小.
结论:
- Pygo2/BRPF1轴代表了COAD中的一个关键的表观遗传漏洞.
- 准BRPF1证明了对Pygo2高的COAD亚型的预测意义和治疗潜力.
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